Transmission electron microscopy (EM) is used as an adjunct procedure in the diagnosis of a wide range of neoplastic and non neoplastic diseases and can be extremely useful in well chosen diagnostic dilemmas. The main objectives of the diagnostic EM service are: (1) to provide EM diagnosis in patient specimens (2) to contribute to the understanding of the pathogenesis of diseases studied in various NIH protocols and (3) to assist investigators in research protocols with specific EM-related questions. The last year's accomplishments are summarized below:(1) A total of 122 patient tissues were processed and diagnosed by EM. Successful CAP inspection occurred on 2/15/00 leading to CAP certification (2) An additional 117 research specimens with multiple samples per specimen were processed and evaluated, resulting in 5 publications. (3) We explored the possibility to use a non radioisotopic in situ polymerase chain reaction at the ultrastrucutral level for the detection of oncogenes. An abstract submitted to the USCAP Academy of Pathology meeting in March of 1999 (Lab Invest 2000; 80:225A (1325)) won honorary mention from the Society of Ultrastructural Pathology (4) Immuno EM was introduced to assist NIH investigators in resolving questions with clinical relevance. Examples and puplications are shown below: (a) Immuno EM labeling showed the human immunodeficiency virus (HIV) envelope protein gp4 to accumulate as an extracellular aggregate in the brains of HIV-infected patients with dementia - Caffrey, M. et al: J Biol Chem 2000; 275:19877-19882 .(b) Immuno EM labeling showed that in patients susceptible to isoflurane-induced hepatitis, isufluorane metabolites bind to liver proteins and are localized in mitochondria- Njoku, D. et al: (Submitted).(c) Immuno EM labeling showed sites of leptin localization in cultured preadipocytes and mature tissue adipocytes- Bornstein, S.R. et al. Diabetes 2000; 49:532-538 .